Dendritic Cells, Obtained from Peripheral Blood Precursors in the Presence of PGE2, Promote Th2 Responses

  • Paweł Kaliński
  • Catharien M. U. Hilkens
  • Alies Snijders
  • Frank G. M. Snijdewint
  • Martien L. Kapsenberg
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 417)

Abstract

In order to investigate the impact of an inflamatory mediator PGE2 on the functions of maturing DC we used an in vitro model of DC generation from peripheral blood monocytes. Addition of PGE, (10−9M–10−6M) to the cultures performed in the presence of GM-CSF and IL-4 did not alter the morphology nor high levels of expression of class II MHC and co-stimulatory molecules on arising DC, although at concentrations above 10−8 M, the acquisition of CD1a was selectively prevented. Control DC and the DC maturing in the presence of PGE2 (PGE,-DC) induced a similar proliferation of naive Th cells. Control DC produced high amounts of IL-12, and only trace amounts of IL-10, whereas PGE2-DC produced no IL-12 and high levels of IL-10, when stimulated after the removal of PGE2. The deficient IL-12 production by PGE2-DC was observed after stimulation both in the absence and in the presence of IFNy, and was not compensated during further 48 h culture in the absence of PGE2. Compared to control DC, PGE2-DC induced development of Th cells secreting elevated amounts of IL-4 and IL-5, from naive precursors. These data indicate that elevated tissue levels of PGE, may promote type 2 Th responses by impairing the ability of locally maturing DC to produce IL-12. Since Th2 responses mediate protection in Thl-related autoimmune disorders, the use of PGE2-DC in immunotherapy of such disorders may be considered.

Keywords

Dendritic Cell Atopic Dermatitis Lepromatous Leprosy Similar Proliferation Potent Stimulatory Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Kaplan, G., G. Walsh, L.S. Guido, P. Meyn, R.A. Burkhardt, R.M. Abalos, J. Barker, P.A. Frindt, T.T. Fajardo, R. Celona, and Z.A. Cohn. 1992. Novel responses of human skin to intradermal recombinant granulocyte/macrophage colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth and enhanced wound healing. J. Ezp. Med. 175: 1717–1728.CrossRefGoogle Scholar
  2. 2.
    Peters, J.H., R.K.H. Gieseler, B. Thiele, and F. Steinbach. 1996. Dendritic cells: from ontogenetic orphans to myelomonocytic descendants. Immunol.Today 17: 273–278.PubMedCrossRefGoogle Scholar
  3. 3.
    Fogh, K., T. Herlin, and K. Kragballe. 1989. Eicosanoids in skin of patients with atopic dermatitis: prostaglandin E2 and leukotriene B4 are present in biologically active concentrations. J. Allergy Clin. lnmonot. 83: 450–457.CrossRefGoogle Scholar
  4. 4.
    Misra, N., M. Selvakumar, S. Singh, M. Bharadwaj, V. Ramesh, R.S. Misra, and I. Nath. 1995. Monocyte derived IL-10 and PGE2 are associated with the absence of Thl cells and in vitro T cell suppression in lepromatous leprosy. lmmunol. Lett. 48: 123–128.CrossRefGoogle Scholar
  5. 5.
    Foley, P., F. Kazazi, R. Biti, C. Sorrel, and A.L. Cunningham. 1992. HIV infection of monocytes inhibits the T-lymphocyte proliferative response to recall antigens, via production of eicosanoids. Immunology 75: 391–397.PubMedGoogle Scholar
  6. 6.
    Snijdewint, E.G., P. Kalinski, E.A. Wierenga, J.D. Bos, and M.L. Kapsenberg. 1993. Prostaglandin E2 differentially modulates cytokine secretion profiles of human T helper lymphocytes. J. Immunol. 150: 5321–5329.PubMedGoogle Scholar
  7. 7.
    van der Pouw Kraan, T.C., L.C. Boeije, R.J. Smeenk. J. Wijdenes, and L.A. Aarden. 1995. Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production. J. Exp. Med. 181: 775–779.CrossRefGoogle Scholar
  8. 8.
    Sallusto, F. and A. Lanzavecchia. 1994. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor α. J. Exp. Med. 179: 1109–1118.PubMedCrossRefGoogle Scholar
  9. 9.
    Fanslow, W.C., S. Srinivasan, R. Paxton, M.G. Gibson, M.K. Spriggs, and M.J. Armitage. 1994. Structural characteristics of CD40 ligand that determine biological function. Seminars Immunol 6: 267CrossRefGoogle Scholar
  10. 10.
    Kalinski, P., C.M. Hilkens, E.A. Wierenga, T.C. van der Pouw-Kraan, R.A. van Lier, J.D. Bos, M.L. Kapsenberg, and F.G. Snijdewint. 1995. Functional maturation of human naive T helper cells in the absence of accessory cells. Generation of IL-4-producing T helper cells does not require exogenous IL-4. J. Immunol. 154: 3753–3760.PubMedGoogle Scholar
  11. 11.
    Nygard, G., A. Larsson, B. Gerdin, S. Ejerblad, and T. Berglindh. 1992. Viability, prostaglandin E2 production, and protein handling in normal and inflamed human colonic mucosa cultured for up to 48 h in vitro. Scand. J Gaslroenterol. 27: 303–310.CrossRefGoogle Scholar
  12. 12.
    Pugh, S. and G.A. Thomas. 1994. Patients with adenomatous polyps and carcinomas have increased colonic mucosal prostaglandin E2. Gut 35: 675–678.PubMedCrossRefGoogle Scholar
  13. 13.
    Schrey, M.P. and K.V. Patel. 1995. Prostaglandin E2 production and metabolism in human breast cancer cells and breast fibroblasts. Regulation by inflammatory mediators. Br J. Cancer 72: 1412–1419.PubMedCrossRefGoogle Scholar
  14. 14.
    Graeme-Cook, F., A.K. Bhan, and N.L. Harris. 1993. Immunohistochemical characterization of intraepithelial and subepithelial mononuclear cells of the upper airways. Am. J. Pathol. 143: 1416–1422.PubMedGoogle Scholar
  15. 15.
    van Haarst, J.M.W., H.C. Hoogsteden, H.J. de Wit, G.T. Verhoeven, C.E.G. Havenith, and H.A. Drexhage. 1994. Dendritic cells and their precursors isolated from human bronchoalveolar lavage: immunocytologic and functional properties. Am. J. Respir: Cell Mol. Biol. 11: 344–350.CrossRefGoogle Scholar
  16. 16.
    Cerio, R., C.E.M. Griffiths, K.D. Cooper, B.J. Nickoloff, and J.T. Headington. 1989. Characterization of factor Xllla positive dermal dendritic cells in normal and inflamed skin. Br. J. Dermatol. 121: 421–431.PubMedCrossRefGoogle Scholar
  17. 17.
    Liblau, S.R., S.M. Singer, and H.O.McDevitt. 1995. Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol. Today 16: 34–42.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Paweł Kaliński
    • 1
  • Catharien M. U. Hilkens
    • 1
  • Alies Snijders
    • 1
  • Frank G. M. Snijdewint
    • 1
  • Martien L. Kapsenberg
    • 1
  1. 1.Department of Cell Biology and Histology Academic Medical CentreUniversity of AmsterdamAmsterdamThe Netherlands

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